Project Summary This cooperative agreement (U01) application responds to NIH RFA-DA-15-015, Adolescent Brain Cognitive Development (ABCD) study, 5/9 Research Site of the Prospective Research in Studies of Maturation (PRISM) Consortium. The Consortium's objective is to establish a national, multisite, longitudinal cohort to prospectively examine the neurodevelopmental and behavioral effects of substance use (SU) from early adolescence through the period of risk for SU and SU disorders. This 10-year longitudinal study of 11,000 children will measure brain development, SU, cognition, emotion, executive function, mental health, physical health, environment, and collect biospecimens for future genetics and epigenetic studies. The Consortium has an optimized research protocol and 4 specific aims: 1) Using advanced multi-modal neuroimaging to evaluate premorbid factors and the impact associated with diverse patterns of SU on the structure and function of the developing brain. 2) Disentangle the predictors and consequences of diverse patterns of SU on physical health, psychosocial and cognitive development, academic achievement, motivation and emotional regulation. 3) Examine how the quantity and combination of substances used affect the expression of psychopathology and, conversely, how the emergence of psychopathology influences SU. 4) Assess how each substance used contributes to the use of other substances (gateway interactions). The Utah site has three sets of specific aims involving (1) Imaging; (2) Family/Genetics; and (3) Special Populations. Imaging Aims: (a) participation in the MRS/QSM substudy with JHU and UH (see JHU project for details) and (b) participation in the perfusion imaging substudy along with Penn, UCLA, and UH (see Penn project for details). Family/Genetics Aims: (a) Cross register all Utah subjects with data contained in the Utah Population Database (UPDB: http://healthcare.utah.edu/huntsmancancerinstitute/research/updb/, the UPDB is the only database of its kind in the United States and one of few such resources in the world). The central component of the UPDB is an extensive set of Utah family histories, in which family members are linked to demographic and medical information and (b) over-enroll siblings, which is made possible by the large family size and the relatively short inter-pregnancy interval of Utahns. Special Population Aims: (a) evaluate a unique adolescent population, those who use marijuana but who have never used other drugs and (b) over-enroll Native American participants, who are known to have substantially higher rates of alcohol-related mortality. Our site is uniquely qualified to be part of the Consortium because of our extensive experience with cognitive assessment and imaging studies of drug-using youth. In addition, the UPDB creates an unprecedented research opportunity at our site. We believe that our contributions in these areas complement those of other outstanding consortium members to collectively achieve the overall goals of the PRISM Consortium.